{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T23:16:16Z","timestamp":1794611776456,"version":"4.9.1"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T00:00:00Z","timestamp":1600300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T00:00:00Z","timestamp":1600300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["SERB\/EMR\/2016\/001000."],"award-info":[{"award-number":["SERB\/EMR\/2016\/001000."]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Self-regulating temperature-controlled nanoparticles such as Mn\u2013Zn ferrite nanoparticles based magnetic fluid can be a better choice for magnetic fluid hyperthermia because of its controlled regulation of hyperthermia temperature window of 43\u201345\u00a0\u00b0C. To test this hypothesis magnetic fluid with said properties was synthesized, and its effect on cervical and breast cancer cell death was studied. We found that the hyperthermia window of 43\u201345\u00a0\u00b0C was maintained for one hour at the smallest possible concentration of 0.35\u00a0mg\/mL without altering the magnetic field applicator parameters. Their hyperthermic effect on HeLa and MCF7 was investigated at the magnetic field of 15.3\u00a0kA\/m and frequency 330\u00a0kHz, which is close to the upper safety limit of 5\u2009*\u200910\n                    <jats:sup>9<\/jats:sup>\n                    \u00a0A\/m\u00a0s. We have tested the cytotoxicity of synthesized Mn\u2013Zn ferrite fluid using MTT assay and the results were validated by trypan blue dye exclusion assay that provides the naked eye microscopic view of actual cell death. Since cancer cells tend to resist treatment and show re-growth, we also looked into the effect of multiple sessions hyperthermia using a 24\u00a0h window till 72\u00a0h using trypan blue assay. The multiple sessions of hyperthermia showed promising results, and it indicated that a minimum of 3 sessions, each of one-hour duration, is required for the complete killing of cancer cells. Moreover, to simulate an in vivo cellular environment, a phantom consisting of magnetic nanoparticles dispersed in 1 and 5% agarose gel was constituted and studied. These results will help to decide the magnetic fluid based hyperthermic therapeutic strategies using temperature-sensitive magnetic fluid.\n                  <\/jats:p>","DOI":"10.1038\/s41598-020-71552-3","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T17:28:45Z","timestamp":1600363725000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["In vitro hyperthermic effect of magnetic fluid on cervical and breast cancer cells"],"prefix":"10.1038","volume":"10","author":[{"given":"Anand","family":"Bhardwaj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinnari","family":"Parekh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Jain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,17]]},"reference":[{"key":"71552_CR1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s11060-010-0389-0","volume":"103","author":"K Maier-Hauff","year":"2011","unstructured":"Maier-Hauff, K. et al. Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J. Neurooncol. 103, 317\u2013324 (2011).","journal-title":"J. Neurooncol."},{"key":"71552_CR2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/02656730601175479","volume":"23","author":"M Johannsen","year":"2007","unstructured":"Johannsen, M. et al. Morbidity and quality of life during thermotherapy using magnetic nanoparticles in locally recurrent prostate cancer: results of a prospective phase I trial. Int. J. Hyperth. 23, 315\u2013323 (2007).","journal-title":"Int. J. Hyperth."},{"key":"71552_CR3","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S0360-3016(00)00650-7","volume":"48","author":"B Rau","year":"2000","unstructured":"Rau, B. et al. Preoperative radiochemotherapy in locally advanced or recurrent rectal cancer: regional radiofrequency hyperthermia correlates with clinical parameters. Int. J. Radiat. Oncol. Biol. Phys. 48, 381\u2013391 (2000).","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"71552_CR4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep42783","volume":"7","author":"M Ohtake","year":"2017","unstructured":"Ohtake, M. et al. Hyperthermia and chemotherapy using Fe(Salen) nanoparticles might impact glioblastoma treatment. Sci. Rep. 7, 1\u201312 (2017).","journal-title":"Sci. Rep."},{"key":"71552_CR5","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12938-017-0327-x","volume":"16","author":"EYK Ng","year":"2017","unstructured":"Ng, E. Y. K. & Kumar, S. D. Physical mechanism and Modeling of heat generation and transfer in magnetic fluid hyperthermia through N\u00e9elian and Brownian relaxation: a review. Biomed. Eng. Online 16, 36 (2017).","journal-title":"Biomed. Eng. Online"},{"key":"71552_CR6","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/S0304-8853(02)00706-0","volume":"252","author":"RE Rosensweig","year":"2002","unstructured":"Rosensweig, R. E. Heating magnetic fluid with alternating magnetic field. J. Magn. Magn. Mater. 252, 370\u2013374 (2002).","journal-title":"J. Magn. Magn. Mater."},{"key":"71552_CR7","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3390\/pharmaceutics11060273","volume":"11","author":"GR Iglesias","year":"2019","unstructured":"Iglesias, G. R. et al. Enhancement of magnetic hyperthermia by mixing synthetic inorganic and biomimetic magnetic nanoparticles. Pharmaceutics 11, 273 (2019).","journal-title":"Pharmaceutics"},{"key":"71552_CR8","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jmmm.2015.03.085","volume":"387","author":"RR Shah","year":"2015","unstructured":"Shah, R. R., Davis, T. P., Glover, A. L., Nikles, D. E. & Brazel, C. S. Impact of magnetic field parameters and iron oxide nanoparticle properties on heat generation for use in magnetic hyperthermia. J. Magn. Magn. Mater. 387, 96\u2013106 (2015).","journal-title":"J. Magn. Magn. Mater."},{"key":"71552_CR9","first-page":"1","volume":"8","author":"KS Sharma","year":"2018","unstructured":"Sharma, K. S. et al. Synthesis and characterization of monodispersed water dispersible Fe3O4 nanoparticles and in vitro studies on human breast carcinoma cell line under hyperthermia condition. Sci. Rep. 8, 1\u201311 (2018).","journal-title":"Sci. Rep."},{"key":"71552_CR10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/srep02887","volume":"3","author":"LC Branquinho","year":"2013","unstructured":"Branquinho, L. C. et al. Effect of magnetic dipolar interactions on nanoparticle heating efficiency: implications for cancer hyperthermia. Sci. Rep. 3, 20\u201322 (2013).","journal-title":"Sci. Rep."},{"key":"71552_CR11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-40769-2","volume":"9","author":"L Le\u00f3n F\u00e9lix","year":"2019","unstructured":"Le\u00f3n F\u00e9lix, L. et al. Gold-decorated magnetic nanoparticles design for hyperthermia applications and as a potential platform for their surface-functionalization. Sci. Rep. 9, 1\u201311 (2019).","journal-title":"Sci. Rep."},{"key":"71552_CR12","doi-asserted-by":"crossref","first-page":"5042","DOI":"10.1039\/b708156a","volume":"17","author":"NK Prasad","year":"2007","unstructured":"Prasad, N. K., Rathinasamy, K., Panda, D. & Bahadur, D. Mechanism of cell death induced by magnetic hyperthermia with nanoparticles of \u03b3-MnxFe2\u2013xO3 synthesized by a single step process. J. Mater. Chem. 17, 5042 (2007).","journal-title":"J. Mater. Chem."},{"key":"71552_CR13","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s12206-015-1053-6","volume":"30","author":"MM Attar","year":"2016","unstructured":"Attar, M. M., Haghpanahi, M., Shahverdi, H. & Imam, A. Thermo-mechanical analysis of soft tissue in local hyperthermia treatment. J. Mech. Sci. Technol. 30, 1459\u20131469 (2016).","journal-title":"J. Mech. Sci. Technol."},{"key":"71552_CR14","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.ceramint.2015.09.103","volume":"42","author":"M Arana","year":"2016","unstructured":"Arana, M., Bercoff, P. G., Jacobo, S. E., Z\u00e9lis, P. M. & Pasquevich, G. A. Mechanochemical synthesis of MnZn ferrite nanoparticles suitable for biocompatible ferrofluids. Ceram. Int. 42, 1545\u20131551 (2016).","journal-title":"Ceram. Int."},{"key":"71552_CR15","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jallcom.2018.02.174","volume":"745","author":"SV Jadhav","year":"2018","unstructured":"Jadhav, S. V. et al. Induction heating and in vitro cytotoxicity studies of MnZnFe2O4 nanoparticles for self-controlled magnetic particle hyperthermia. J. Alloys Compd. 745, 282\u2013291 (2018).","journal-title":"J. Alloys Compd."},{"key":"71552_CR16","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1021\/acs.jpcc.7b11014","volume":"122","author":"V Pilati","year":"2018","unstructured":"Pilati, V. et al. Core\/shell nanoparticles of non-stoichiometric Zn-Mn and Zn-Co ferrites as thermosensitive heat sources for magnetic fluid hyperthermia. J. Phys. Chem. C 122, 3028\u20133038 (2018).","journal-title":"J. Phys. Chem. C"},{"key":"71552_CR17","first-page":"1","volume":"7","author":"B Rau","year":"2018","unstructured":"Rau, B. et al. Effects of Mn concentration on the ac magnetically induced heating characteristics of superparamagnetic MnxZn1-xFe 2O4 nanoparticles for hyperthermia. Sci. Rep. 7, 1\u201311 (2018).","journal-title":"Sci. Rep."},{"key":"71552_CR18","first-page":"8390","volume":"B2","author":"A Makridis","year":"2014","unstructured":"Makridis, A. et al. In vitro application of Mn-ferrite nanoparticles as novel magnetic hyperthermia agents. J. Mater. Chem. B2, 8390\u20138398 (2014).","journal-title":"J. Mater. Chem."},{"key":"71552_CR19","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3390\/nano5010063","volume":"5","author":"IM Obaidat","year":"2015","unstructured":"Obaidat, I. M., Issa, B. & Haik, Y. Magnetic properties of magnetic nanoparticles for efficient hyperthermia. Nanomaterials 5, 63 (2015).","journal-title":"Nanomaterials"},{"key":"71552_CR20","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jmmm.2016.08.024","volume":"431","author":"K Parekh","year":"2017","unstructured":"Parekh, K. & Upadhyay, R. V. The effect of magnetic field induced aggregates on ultrasound propagation in aqueous magnetic fluid. J. Magn. Magn. Mater. 431, 74\u201378 (2017).","journal-title":"J. Magn. Magn. Mater."},{"key":"71552_CR21","volume-title":"Electromagnetic Field Theory: A Problem Solving Approach","author":"M Zahn","year":"2003","unstructured":"Zahn, M. Electromagnetic Field Theory: A Problem Solving Approach (Krieger Publishing Company, Malabar, 2003)."},{"key":"71552_CR22","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1186\/s11671-015-1091-0","volume":"10","author":"C Iacovita","year":"2015","unstructured":"Iacovita, C. et al. Polyethylene glycol mediated synthesis of cubic iron oxide nanoparticles with high heating power. Nanoscale Res. Lett. 10, 391 (2015).","journal-title":"Nanoscale Res. Lett."},{"key":"71552_CR23","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1103\/PhysRev.56.978","volume":"56","author":"AL Patterson","year":"1939","unstructured":"Patterson, A. L. The Scherrer formula for x-ray particle size determination. Phys. Rev. 56, 978\u2013982 (1939).","journal-title":"Phys. Rev."},{"key":"71552_CR24","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4899-0148-4","volume-title":"X-Ray Diffraction: A Practical Approach","author":"C Suryanarayana","year":"1998","unstructured":"Suryanarayana, C. & Norton, M. G. X-Ray Diffraction: A Practical Approach (Springer, Berlin, 1998)."},{"key":"71552_CR25","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.jmmm.2007.08.010","volume":"320","author":"J Giri","year":"2008","unstructured":"Giri, J. et al. Synthesis and characterizations of water-based ferrofluids of substituted ferrites [Fe1-xBxFe2O4, B=Mn, Co (x=0-1)] for biomedical applications. J. Magn. Magn. Mater. 320, 724\u2013730 (2008).","journal-title":"J. Magn. Magn. Mater."},{"key":"71552_CR26","doi-asserted-by":"crossref","first-page":"7533","DOI":"10.3390\/molecules18077533","volume":"18","author":"M Mahdavi","year":"2013","unstructured":"Mahdavi, M. et al. Synthesis, surface modification and characterisation of biocompatible magnetic iron oxide nanoparticles for biomedical applications. Molecules 18, 7533\u20137548 (2013).","journal-title":"Molecules"},{"key":"71552_CR27","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/jbm.b.30630","volume":"81B","author":"P Pradhan","year":"2007","unstructured":"Pradhan, P. et al. Comparative evaluation of heating ability and biocompatibility of different ferrite-based magnetic fluids for hyperthermia application. J. Biomed. Mater. Res. Part B Appl. Biomater. 81B, 12\u201322 (2007).","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"71552_CR28","doi-asserted-by":"crossref","first-page":"11640","DOI":"10.1021\/acs.jpcc.5b12476","volume":"120","author":"R Lenin","year":"2016","unstructured":"Lenin, R. & Joy, P. A. Role of primary and secondary surfactant layers on the thermal conductivity of lauric acid coated magnetite nanofluids. J. Phys. Chem. C 120, 11640\u201311651 (2016).","journal-title":"J. Phys. Chem. C"},{"key":"71552_CR29","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1016\/j.jmmm.2008.11.098","volume":"321","author":"K Maaz","year":"2009","unstructured":"Maaz, K. et al. Synthesis and magnetic characterization of nickel ferrite nanoparticles prepared by co-precipitation route. J. Magn. Magn. Mater. 321, 1838\u20131842 (2009).","journal-title":"J. Magn. Magn. Mater."},{"key":"71552_CR30","doi-asserted-by":"crossref","first-page":"5970","DOI":"10.1088\/0957-4484\/17\/24\/011","volume":"17","author":"K Parekh","year":"2006","unstructured":"Parekh, K., Upadhyay, R. V., Belova, L. & Rao, K. V. Ternary monodispersed Mn0.5Zn0.5Fe2O4 ferrite nanoparticles: preparation and magnetic characterization. Nanotechnology 17, 5970\u20135975 (2006).","journal-title":"Nanotechnology"},{"key":"71552_CR31","doi-asserted-by":"crossref","unstructured":"Eberbeck, D. et al. Quantification of the aggregation of magnetic nanoparticles with different polymeric coatings in cell culture medium. J. Phys. D. Appl. Phys. 43 (2010).","DOI":"10.1088\/0022-3727\/43\/40\/405002"},{"key":"71552_CR32","doi-asserted-by":"crossref","first-page":"495003","DOI":"10.1088\/0022-3727\/47\/49\/495003","volume":"47","author":"RR Wildeboer","year":"2014","unstructured":"Wildeboer, R. R., Southern, P. & Pankhurst, Q. A. On the reliable measurement of specific absorption rates and intrinsic loss parameters in magnetic hyperthermia materials. J. Phys. D. Appl. Phys. 47, 495003 (2014).","journal-title":"J. Phys. D. Appl. Phys."},{"key":"71552_CR33","doi-asserted-by":"crossref","first-page":"166057","DOI":"10.1016\/j.jmmm.2019.166057","volume":"497","author":"K Parekh","year":"2020","unstructured":"Parekh, K., Bhardwaj, A. & Jain, N. preliminary in-vitro investigation of magnetic fluid hyperthermia in cervical cancer cells. J. Magn. Magn. Mater. 497, 166057 (2020).","journal-title":"J. Magn. Magn. Mater."},{"key":"71552_CR34","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","volume":"65","author":"T Mosmann","year":"1983","unstructured":"Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55\u201363 (1983).","journal-title":"J. Immunol. Methods"},{"key":"71552_CR35","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/0471142735.ima03bs21","volume":"21","author":"W Strober","year":"2001","unstructured":"Strober, W. Trypan blue exclusion test of cell viability. Curr. Protoc. Immunol. 21, 2\u20133. https:\/\/doi.org\/10.1002\/0471142735.ima03bs21 (2001).","journal-title":"Curr. Protoc. Immunol."},{"key":"71552_CR36","doi-asserted-by":"crossref","first-page":"9064","DOI":"10.1021\/la900833v","volume":"25","author":"B Chanteau","year":"2009","unstructured":"Chanteau, B., Fresnais, J. & Berret, J. F. Electrosteric enhanced stability of functional sub-10 nm cerium and iron oxide particles in cell culture medium. Langmuir 25, 9064\u20139070 (2009).","journal-title":"Langmuir"},{"key":"71552_CR37","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1021\/jp907046f","volume":"114","author":"A Villanueva","year":"2010","unstructured":"Villanueva, A. et al. Hyperthermia HeLa cell treatment with silica-coated manganese oxide nanoparticles. J. Phys. Chem. C 114, 1976\u20131981 (2010).","journal-title":"J. Phys. Chem. C"},{"key":"71552_CR38","first-page":"1042","volume":"11","author":"EI Gkanas","year":"2013","unstructured":"Gkanas, E. I. In vitro magnetic hyperthermia response of iron oxide MNP\u2019s incorporated in DA3, MCF-7 and HeLa cancer cell lines. Cent. Eur. J. Chem. 11, 1042\u20131054 (2013).","journal-title":"Cent. Eur. J. Chem."},{"key":"71552_CR39","doi-asserted-by":"crossref","first-page":"47225","DOI":"10.1039\/C5RA04553C","volume":"5","author":"RA Bohara","year":"2015","unstructured":"Bohara, R. A., Thorat, N. D., Chaurasia, A. K. & Pawar, S. H. Cancer cell extinction through a magnetic fluid hyperthermia treatment produced by superparamagnetic Co-Zn ferrite nanoparticles. RSC Adv. 5, 47225\u201347234 (2015).","journal-title":"RSC Adv."},{"key":"71552_CR40","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.msec.2015.10.064","volume":"59","author":"RM Patil","year":"2016","unstructured":"Patil, R. M. et al. In vitro hyperthermia with improved colloidal stability and enhanced SAR of magnetic core\/shell nanostructures. Mater. Sci. Eng. C 59, 702\u2013709 (2016).","journal-title":"Mater. Sci. Eng. C"},{"key":"71552_CR41","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.msec.2016.05.086","volume":"68","author":"RR Shah","year":"2016","unstructured":"Shah, R. R. et al. Determining iron oxide nanoparticle heating efficiency and elucidating local nanoparticle temperature for application in agarose gel-based tumor model. Mater. Sci. Eng. C 68, 18\u201329 (2016).","journal-title":"Mater. Sci. Eng. C"},{"key":"71552_CR42","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.jmmm.2018.09.111","volume":"471","author":"M Avolio","year":"2019","unstructured":"Avolio, M. et al. In-gel study of the effect of magnetic nanoparticles immobilization on their heating efficiency for application in magnetic fluid hyperthermia. J. Magn. Magn. Mater. 471, 504\u2013512 (2019).","journal-title":"J. Magn. Magn. Mater."},{"key":"71552_CR43","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jmmm.2009.09.006","volume":"322","author":"S Chen","year":"2010","unstructured":"Chen, S., Chiang, C. L. & Hsieh, S. Simulating physiological conditions to evaluate nanoparticles for magnetic fluid hyperthermia (MFH) therapy applications. J. Magn. Magn. Mater. 322, 247\u2013252 (2010).","journal-title":"J. Magn. Magn. Mater."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71552-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71552-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71552-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T13:35:41Z","timestamp":1670333741000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71552-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,17]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["71552"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-71552-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,17]]},"assertion":[{"value":"24 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15249"}}